The family of the Flaviviridae consists of 3 genera, the pestiviruses, the flaviviruses and the hepaciviruses and also contains the hepatitis G virus (HGV/GBV-C) that has not yet been assigned to a genus.
Pestiviruses such as the Classical Swine Fever Virus (CSFV), the Bovine Viral Diarrhea Virus (BVDV) and the Border Disease Virus (BDV) cause infections of domestic livestock (respectively pigs, cattle and sheep) and are responsible for significant economic losses world-wide. BVDV, the prototypic representative of the pestivirus genus is ubiquitous and causes a range of clinical manifestations, including abortion, teratogenesis, respiratory problems, chronic wasting disease, immune system dysfunction, and predisposition to secondary viral and bacterial infections and may also cause acute fatal disease. Foetuses of cattle can be infected persistently with BVDV, these animals remain viremic throughout life and serve as a continuous sources for virus spread in herds.
Vaccines are used in some countries with varying degrees of success to control pestivirus disease. In other countries, animal culling and slaughter are used to contain pestivirus disease outbreaks.
The compound 3-[((2-dipropylamino)ethyl)thio]-5H-1,2,4-triazino[5,6-b]indole (VP32947) has been reported to selectively inhibit the replication of BVDV and other pestiviruses (Baginski S G and al., Proc. Natl. Acad. Sci. U.S.A. 2000 Jul. 5; 97(14):7981-6). Also 5-[(4-bromophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine (BPIP), has recently been described as possessing potent anti-pestivirus activity. Currently, there is no treatment strategy available on the market for controlling infections caused by pestiviruses.
Therefore, there is a need for novel, potent compounds which show antiviral activity against Flaviviridae, more specifically against Pestiviruses.
The present invention provides for novel compounds which show activity against viruses, more specifically against Flaviviridae. There is a clear need in the field for alternative antiviral compounds, furthermore with a good activity vs toxicity profile and this specifically for the viruses of the family of the Flaviviridae, more specifically for Pestiviruses. The prior art does not lead a person skilled in the art to the compounds of the present invention and to their use as antiviral compounds.